Monoclonal B-cell lymphocytosis as a biomarker in environmental health studies

Summary The first studies of monoclonal B-cell lymphocytosis (MBL) inthe general population were conducted as part of environ-mental health investigations that began in 1991. MBL wasobserved as an unexpected finding when blood samples wereimmunophenotyped by two-colour flow cytometric methodsin common use at that time. The initial observations led toa workshop in 1995, at which case definitions were consideredand medical follow-up investigations were recommended.Medical follow-ups were conducted in 1997 and 2003. A totalof eight cases of confirmed MBL and three cases of presump-tive MBL were identified. This review summarizes the findingsfrom those investigations and discusses the issues related tousing MBL as a biomarker in environmental health researchand population-based studies.Keywords: hazardous waste, B-cell lymphoproliferative disor-ders, chronic lymphocytic leukaemia, aetiology, epidemiology.Epidemiological studies of chronic lymphocytic leukaemia(CLL) are complicated by a prolonged asymptomatic period.As most CLL is diagnosed after an incidental haematologicallaboratory finding (Rozman & Montserrat, 1995), its apparentprevalence in a population depends on the extent to whichblood counts have been performed. Even if it has beendiagnosed, CLL may not be indicated on the death certificatewhen a subject dies of an unrelated cause. Moreover, CLL maynot be included in the death certificates of those who diedfrom closely related causes, such as infectious disease orhaemorrhage. Detection of the preclinical condition recentlytermed monoclonal B-cell lymphocytosis (MBL) (Marti et al,2005) is completely dependent on laboratory evaluation: itrequires sophisticated flow cytometry with immunophenotyp-ing for surface receptor expression and kappa-lambda analysis.Consequently, environmental factors that increase the risk ofMBL or CLL will go unrecognized in epidemiological inves-tigations without analysing peripheral blood samples usingmethods designed to detect monoclonal B-cell populations.Because the laboratory procedures required for the detectionof MBL and CLL are specialized and somewhat costly, they arerarely used to evaluate large residential populations. Anopportunity to conduct a large-scale evaluation was presentedby a series of environmental health studies conducted aroundhazardous waste sites and in comparison communitiesbetween 1991 and 1994 (Sarasua et al, 1997). While analysingblood samples from residents of these communities, weidentified 11 individuals with a B-cell clone by kappa-lambdaanalysis or surface receptor expression patterns (Marti et al,1997a; Vogt et al, 1997). Two additional cases with a B-cellclone were discovered during two follow-up studies conductedafter the original investigations (Shim et al, 2007). This reportreviews the findings from these previous studies and considerstheir implications for environmental health research andclinical haematology practice. We also contemplate the futurestudies needed to characterise the relationship between envi-ronmental exposures and B-cell malignancies.